The objective of this research is to provide increased understanding of metabolic control in heart tissue and the mecahnism of enzyme regulation. This will be achieved by intensive study of the kinetic and physical properties of mitochondrial malate dehydrogenase, one of the key enzymes in oxidative metabolism. Anomalous kinetic features and the effects of various metabolites on the reaction mechanism will be studied in detail, with particular emphasis on transient kinetics. Binding studies and the evaluation of conformational interactions by fluorescence techniques will complement the kinetic studies. It is anticipated that this project will result in determination of effectors which can modify the malate dehydrogenase reaction as well as further information on the mechanism of allosteric interactions.